The effects of isoproterenol, a beta-adrenoceptor agonist, on the production of interleukin-1beta in the brain and on mechanical nociception were examined in rats. Intracerebroventricular (i.c.v.) injection of isoproterenol at the dose of 3 microg/rat markedly induced interleukin-1beta mRNA in the molecular layer of the hippocampus, medial preoptic area, paraventricular thalamic nucleus, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus and central gray 1 h after injection. In these regions, interleukin-1beta mRNA was expressed mainly in the glial cells. The thresholds to the mechanical stimulation to the hind paw were elevated by i.c.v. administration of isoproterenol (1 to 10 microg/rat). When isoproterenol was given at the dose of 3 microg/rat, the analgesic effect showed two peaks. The first peak was observed at 60 min after injection and the second was observed at 180 min. The second phase of analgesia was antagonized by coadministration of interleukin-1 receptor antagonist. These results suggest that isoproterenol produces an analgesic effect, at least in part, through the induction of interleukin-1beta expression in the brain.